Unexpected reactions and novel glycosylations with benzotriazole and nitrophenyl derivatives [Elektronische Ressource] = Ungewöhnliche Reaktionen und neuartige Glycosylierungen mit Benzotriazol- und Nitrobenzolderivaten / vorgelegt von Xavier Àlvarez Micó

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Informations

• Publié par: eberhard_karls_universitat_tubingen
• Publié le: 01 janvier 2006
• Nombre de lectures: 11
• Langue: Deutsch

Extrait

Unexpected reactions and novel
glycosylations with benzotriazole and
nitrophenyl derivatives
Ungewöhnliche Reaktionen und
neuartige Glycosylierungen mit
Benzotriazol- und Nitrobenzolderivaten
DISSERTATION
der Fakultät für Chemie und Pharmazie
der Eberhard-Karls-Universität Tübingen
zur Erlangung des Grades eines Doktors
der Naturwissenschaften
2006
vorgelegt von
Xavier Àlvarez MicóTag der mündlichen Prüfung: 11. April 2006
Dekan: Prof. Dr. S. Laufer
1. Berichterstatter: Prof. Dr. Th. Ziegler
2. Berichterstatter: Prof. Dr. M. E. Maier Simone und meiner Familie in
Liebe und Dankbarkeit gewidmet Mein herzlicher Dank gilt:
Herrn Prof. Dr. Th. Ziegler für die Überlassung des Themas und die hervorragende
Betreuung und Förderung in Rahmen dieser Arbeit durch zahlreiche Anregungen
und Diskussionen.
Herrn Prof. Dr. M. E. Maier für seine Tätigkeit als Mitberichter.
Den Herren Dr. L. R. Subramanian, Dr. G. Lemanski, Dr. M. Calvete und Dr. S.
Vagin sowie allen Kollegen und Mitarbeitern in Tübingen für ihre Unterstützung und
die gute Zusammenarbeit.
Frau A. Just für die Durchführung der Elementaranalysen.
Den Herren P. Schuler, B. Maier und Frau P. T. Nguyen für die zahlreichen NMR-
Messungen.
Frau A. Frickenschmidt für die Durchführung der MALDI-TOF Messungen.
Den Herren H. Bartholomä und R. Müller für die Aufnahme zahlreicher
Massenspektren.
Frau S. Schweizer und Herrn Prof. Dr. C. Ochsenfeld für die Berechnungen der
Moleküle. Index
Index
Abbreviations ............................................................................................................iii
1 Introduction and Aim of the Work.....................................................................1
2 General Part.........................................................................................................3
2.1 Overview on Glycosylation................................................................................3
2.1.1 Role of Carbohydrates in Nature ...................................................................3
2.1.2 O-Glycosylation Methods...............................................................................3
2.1.3 Sulfonates as Glycosyl Donors......................................................................7
2.1.4 Direct O-Alkylation and O-Arylation.............................................................12
2.2 Glycosylation with Nonafluorobutanesulfonyl and Unexpected Reactions.....14
2.2.1 Aim of this Work and Synthetic Strategies ..................................................14
2.2.2 Overview on the Uses of Nonafluorobutanesulfonyl Fluoride .....................15
2.2.3 Nonafluorobutanesulfonyl Fluoride for Glycosylation..................................16
2.2.3.1 Methyl 2,3,4,6,-tetra-O-benzyl-( DE )-D-glucopyranoside.........................16
2.2.3.2 2,2’,3,3’,4,4’,6,6’-Octa-O-benzyl-( )-trehalose............................19
2.2.3.3 Reaction Mechanisms..............................................................................20
2.2.4 Nonafluorobutanesulfonyl-1H-1,2,3-benzotriazole......................................22
2.2.4.1 Synthesis of 1-nonafluorobutanesulfonyl-1H-1,2,3-benzotriazole...........22
2.2.4.2 Reaction of 6a with Carbohydrates..........................................................23
2.2.4.3 Reactions with Phenol..............................................................................23
2.2.4.4 with Phenol Derivatives...........................................................26
2.2.4.5 Ring Opening Reaction Mechanism ........................................................28
2.2.5 Unsymmetrically Fused 1,2,3,-triazole-zincphthalocyanine ........................34
2.2.5.1 Synthesis of Naphthyl-azoconjugated Phthalocyanines..........................34
2.2.6 Phosphorus Ylides.......................................................................................37
2.2.6.1 Synthesis with Benzyltriphenylphosphonium Salts..................................37
2.2.6.2 Synthesis with Alkyl Triphenylphosphonium Salts...................................39
2.2.7 Synthesis of Glucosyl 1H- and 2H-benzotriazoles ......................................41
2.2.8 Nonafluorobutanesulfonic acid benzotriazol-1-yl ester ...............................44
i
DDDEEEIndex
2.2.8.1 Synthesis of nonafluorobutanesulfonic acid benzotriazol-1-yl ester ......44
2.2.8.2 Reactions of HOBt Derivatives with Tf O ................................................452
2.2.8.3 Reaction Mechanisms..............................................................................48
2.2.8.4 Derivatisation of 28b ................................................................................49
2.3 Aromatic Nitro Substitution .............................................................................50
2.3.1 Introduction in Photodynamic Therapy........................................................50
2.3.2 Aromatic Nitro Substitution..........................................................................51
2.3.2.1 Nitro Substitution with 4-nitrophthalonitrile .............................................52
2.3.2.2 Nititution with Monoactivated Nitrobenzenes.............................54
2.3.3 Synthesis of Phthalocyanines .....................................................................57
3 Summary............................................................................................................60
4 Experimental Part .............................................................................................63
4.1 General Comments .........................................................................................63
4.2 Experimental Procedures................................................................................66
4.2.1 Related to Chapter 2.2.3 .............................................................................66
4.2.2 Related to Chapter 2.2.4 .............................................................................70
4.2.3 Related to Chapter 2.2.5 .............................................................................82
4.2.4 Related to Chapter 2.2.6 .............................................................................85
4.2.5 Related to Chapter 2.2.7 .............................................................................91
4.2.6 Related to Chapter 2.2.8 .............................................................................95
4.2.7 Related to Chapter 2.3.2 ...........................................................................110
4.2.8 Related to Chapter 2.3.3 ...........................................................................123
5 Crystal Data.....................................................................................................127
6 Compound Numbers ......................................................................................152
7 Literature .........................................................................................................158
iiAbbreviations
Abbreviations
° Degree (Angle) m Medium (IR)
m Multiplet (NMR) Optical rotation
Å Angstrom MALDI Matrix assisted laser desorption
Ac Acetyl ionization
Anal. Analytical Mes Methanesulfonyl
Bn BenzyMesyl
br Broad signal (NMR) mp Melting point
bs Broad singlet (NMR) MP2/ Moller-Plesset second order
Bz Benzoyl perturbation theory
Calcd Calculated MS Mass spectrometry
cc-pVDZ Correlation consistent polarised Wavelength (IR)
valence double zeta (basis set) Nc Naphthalocyanine
cc-pVTZ Correlation consistent polarised NBS N-Bromosuccinimide
valence triple zeta (basis set) Nfonafluorobutanesulfonyl
CE 15-Crown-5 ether NIS N-Iodosuccinimide
COSY Correlation spectroscopy (NMR) NMR Nuclear magnetic resonance
Chemical shift Nonaflyl Nonafluorobutanesulfonyl
d Doublet (NMR) Nos p-Nitrobenzenesulfonyl
D Yellow sodium D line (589 nm) Nu Nucleophile
dd Doublet of doublet Petroleum Petroleum ether65–90°C
DBU 1,8-Diazabyciclo[5.4.0]undec-7- ether
ene Pc Phthalocyanine
DCC N,N-Dicyclohexylcarbodiimide PDThotodynamic therapy
Dec. Decomposition PhthN Phthalimido
DEPT Distortionless enhancement by ppm Part per million
polarisation transfer (NMR) PTSA p-Toluenesulfonic acid
DIAD Diisopropyldiazacarboxylate Pz Porphyrazine
DIC Diisopropylcarbodiimide RT Room temperature
DMAE Dimethylaminoethanol s Strong(IR)
DMF N,N-Dimethylformamide t Triplet(NMR)
DMSO Dimethylsulfoxide t Time
EI Electron impact (MS) T Temperature
EWD Electron withdrawing TBDS tert-Butyldimethylsilyl
FAB Fast atom bombardment (MS) THF Tetrahydrofuran
Glyme 1,2-Dimethoxyethane Tf Trifluoromethanesulfonyl
HOAt 7-Aza-1-hydroxybenzotriazole TfOluoromethanesulfonate
HOBt 1-Hydroxybenzotriazole TLC Thin layer chromatography
HPLC High performance liquid TMS Trimethylsilyl
chromatography Tos p-Toluenesulfonyl
HRMS High resolution mass Tosyl p-Tl
spectrometry TOF Time of flight
Hz Herz Triflyl Trifluoromethanesulfonyl
IDCP Iodonium dicollidine perchlorate UV Ultraviolet
IR Infrared Vis Visible
J Coupling constant vs Very strong (IR)
Wavelength (UV/Vis, X-Ray) vweweak(IR)
LG Leaving group w Weak (IR)
Lit. Literature
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